Prevention of Colonic Preneoplasic Lesions by the β-Cryptoxanthin and Hesperidin Rich Powder Prepared from Citrus Unshiu Marc. Juice in Male F344 Rats

Abstract

The modifying effects of dietary administration of β-cryptoxanthin and hesperidin rich powder (CHRP) on the development of azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF) were investigated in male F344 rats. The effects of CHRP on glutathione S-transferase (GST) and quinone reductase (QR) activities in liver and colonic mucosa of rats gavaged with CHRP (0, 40, 200, and 400 mg/kg body wt) for 5 days were also examined. CHRP containing 0.67% β-cryptoxanthin and 3.58% hesperidin was prepared from Satsuma mandarin (Citrus unshiu Marc.)juice. Rats were given s.c. injections of AOM (20 mg/kg body weight) once a week for 2 weeks to induce ACF. They also received the experimental diet containing 500 ppm CHRP for 4 weeks, starting one week before the first dosing of AOM and maintained on a basal diet CE-2 for 7 weeks. AOM exposure produced 80 ± 3 ACF/rat at week 4 and 119 ± 5 ACF/rat at week 11. Dietary administration of CHRP caused significant reduction in the frequency of ACF: 64 ± 9 (20% reduction, p<0.01) at week 4 and 97 ± 11 (18% reduction, p<0.005) at week 11. Also, the number of cryptal cells positive for proliferative cell nuclear antigen in ACF and surrounding “normal-appearing” crypts were lowered by feeding of CHRP containing diet. In the liver and colon of rats gavaged with CHRP, the activities of GST and QR were significantly elevated. These findings might suggest possible chemopreventive effects of CHRP, through their modulation of the cryptal cell proliferation activity and/or activities of phase II enzymes GST and QR, on colon tumorigenesis.